In-Vitro Release of Ketoprofen Behavior Loaded in ...3) Dalia Hegazy Paper 1.pdfIn-Vitro Release of Ketoprofen Behavior Loaded in Polyvinyl Alcohol / Acrylamide Hydrogels Prepared

Arab Journal of Nuclear Science and Applications, 47(1), (28-40) 2014

28

In-Vitro Release of Ketoprofen Behavior Loaded in Polyvinyl Alcohol /

Acrylamide Hydrogels Prepared by Gamma Irradiation

Ghada A. Mahmoud , Dalia E. Hegazy and H. Kamal National Center for Radiation Research and Technology (NCRRT), P.O. Box 29, Nasr City, Cairo,

Egypt. Received: 25/12/2013 Accepted: 15/1/2014

ABSTRACT

Hydrogels based on various ratios of polyvinyl alcohol (PVA) and acrylamide

(AAm) were prepared by gamma radiation. The formed hydrogels were

characterized by spectroscopic analysis (FTIR), differential scanning calorimetry

(DSC), thermogravimetric analysis (TGA) and swelling studied. It was found that

the thermal stability of the hydrogel decreases as the AAm content increases in the

hydrogel. The higher the AAm content in the hydrogel, the lower the values of Tm

and ΔHm. Ketoprofen was adopted as a model drug to study the adsorption and

release behavior of (PVA/AAm) hydrogel. The drug adsorption was decreased by

increasing AAm ratio in the hydrogel. From the in vitro drug release study in pH

progressive media, the basic medium was showed comparatively the highest release

and the (PVA/AAm) hydrogel of composition (70/30) was found to be the highest

release one. The mechanism of Ketoprofen release from the (PVA/AAm) matrix was

found to be non-Fickian mechanism for all investigated hydrogels at pH 7.

KEY WORDS: hydrogel; Radiation; Ketoprofen; Drug release

INTRODUCTION

Hydrogels are a network of polymer chains that are water-insoluble. Over the decades,

hydrogels have been invented for numerous pharmaceutical and biomedical applications (1.2).

Hydrogels are inherently soft, hydrophilic, porous, and elastic polymeric systems. The use of polymer

hydrogels as biopotential sorbent or carriers for the removal of the model molecules from aqueous

solutions or controlled release studies of them has been continued to attract con-siderable attention in

recent years (3-5).

PVA is an important water soluble polymer (1), it is biocompatible and non-toxic. It absorbs

water, swells easily and it has extensively been used in controlled release applications(6). Therefore, a

number of methods have been reported for preparation of PVA hydrogels, including chemical methods

using a covalent cross-linking agent (7,8), physical methods (9,10) and radiation methods using γ-

radiation(11,12) electron beams (13), or ultraviolet light (14). Radiation polymerization is a useful method

for producing hydrogels(15–17). It provides a very clean process, because no initiator and crosslinker

need to be added to reaction media(18). Moreover, since the hydrogels are not contaminated with

foreign additives, the pore size of hydrogels can be controlled by environmental conditions. AAm

based hydrogels are widely used in the drug release systems (19,20). PVA/AAm hydrogels have good

physical and mechanical properties in addition to their swelling and drug release capabilities (21).

Ketoprofen, 2-(3-benzoylphenyl)-propionic acid, is an analgesic, antipyretic and a non-steroidal

anti-inflammatory drug used for the treatment of rheumatoid arthritis, osteoarthritis and other chronic

musculoskeletal conditions(22,23). Conventional dosage forms of this drug, administered orally, three or

Corresponding author, Email: ghadancrrt@ yahoo.com


29

four doses per day, have side effects such as peptic ulceration or bleeding and anorexia, and some

additional side effects (24) that limit its use. Controlled release of the drug is expected to significantly

mitigate these side effects by targeting only the specific organs in the body. Diffusion in polymers is

an important mechanism in pharmacy for the controlled release of drugs. Diffusion in polymeric

systems is passive, if the driving force is purely a Brownian molecular motion, but diffusion can also

be activated by external effects, either by the influence of the release medium by swelling or by the

effects of physical forces as electrical, osmotic or convective forces (25).

In this study, PVA and AAm were chosen to make the hydrogel by gamma irradiation. The

structural properties of the (PVA/AAM) hydrogels were characterized by different techniques such as

FTIR spectroscopy, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC).

The swelling properties of the hydrogel were investigated. PVA based hydrogel was used as a drug

delivery carriers. The drug delivery will be estimated using Ketoprofen as a model of drug. For this

purpose, the effects of AAm content in the hydrogel, initial feed concentrations of drug and pH of

medium on the release of Ketoprofen were studied.

MATERIALS AND METHODS

1. Materials

Poly(vinyl alcohol) (PVA; Mw 15,000) was purchased from Aldrich Co. and acrylamide

(AAm), obtained from (Merck, Germany)were used as received. Ketoprofen (Sigma chemical Co.,

USA), structure of the drug is shown below. The other chemicals were reagent grade and used without

further purification. The components of the citrate and phosphate buffers were reagent grade and

purchased from El-Nasr Co. for Chemical Industries (Egypt) and used as purchased without further

purification. Distilled water was used in all experiments.

Chemical structure of ketoprofen

2. Preparation of PVA/AAm Hydrogel

The PVA/AAm hydrogels were synthesized by the free radical polymerization. An aqueous

solution of 10% PVA (w/v) was dissolved at 80 oC in water bath with constant stirring for 6 h. After

cooling down to room temperature, various compositions of AAm were added to the solution, where,

the total concentration was of 20% .The resulting solutions were transferred into the glass tube to

irradiate by 60Co gamma source at room temperature with radiation dose 20 kGy. The dose rate of

irradiation was 3.065 kGy h-1 after copolymerization, the vials were broken, the formed polymeric

cylinder were removed and cut into discs of 2 mm thickness and 5 mm diameter. All samples were

washed in excess water to remove the unreacted component then air dried at room temperature.

3. Swelling Measurements

The clean, dried, sample of preweight was soaked in bidistilled water at room temperature for

different intervals time durations. The sample was removed and the excess water on the surface was

removed by blotting quickly with filter paper and weighed. The swelling ratio was calculated as

follows:-

Where Wd and Ws are the masses of dry and wet hydrogel, respectively.


30

4. Fourier Transform Infrared Spectroscopy (FTIR)

IR spectra of the investigated films were recorded over the range 400–4000 cm-1, using a

Mattson 1000, Unicom infrared spectrophotometer (Cambridge, England).

5. Thermogravemetric Analysis (TGA)

Thermogravimetric analysis (TGA) was conducted on a Shimadzu TGA system, Type TGA-50,

under nitrogen flow atmosphere of 20 ml/min to prevent thermal oxidation processes of polymer

samples. The heating rate was 10C/ min from ambient up to 500C.

6. Differential Scanning Calorimetry (DSC)

DSC measurements were performed using a Shimadzu DSC calorimeter (Kyoto, Japan)

equipped with data station. A heating rate of 10 C/min was utilized and the scans were carried out

under a flowing nitrogen gas at a rate of 20 mL/min.

7. Drug Loading to the Hydrogl

The loading of Ketoprofen drug onto PVA/AAm hydrogels were carried out by swelling

equilibrium method. The hydrogels were allowed to swell in the drug solution of known concentration

for 24 h at 37C and then dried at room temperature. The concentration of rejected solution was

measured to calculate the percent entrapment of the drug in the polymer matrix using a Unicam, UV–

Vis Spectrometer, Model 1000 at the wavelength 262 nm. The amount of adsorbate per unit mass of

adsorbent (qe) was calculated as follows:

Where Ci and Ce are the initial and equilibrium concentrations of adsorbate solution in mg/ml.

8. In-Vitro Release Studies

In vitro release studies of the drug were performed by placing the pre-weighed hydrogels loaded

with Ketoprofen drug in definite volume of releasing medium of buffer at pH 1.5 at 37C for 3 h and

subsequently in buffer of pH 7 at 37 C for 24 h. One milliliter sample was withdrawn on time

intervals to follow the release process. The concentration of Ketoprofen drugs was measured. After the

complete release; the hydrogels were immersed in pH 3.0 buffer solution and then, 0.1mol/L, HCl for

2 days to remove the remaining drug which may be loaded in the gel system. The total uncertainly for

all experiments ranged from 3to 5%.

RESULTS AND DISCUSSION

The prepared PVA/AAm hydrogels using γ-radiation copolymerization technique as mentioned in

the experimental part were then subjected to different characterization techniques; including FT-IR,

TGA, DSC and swelling behaviors.

1. FT-IR Analysis

FT-IR spectra of PVA and (PVA/ AAm) hydrogels are shown in Figure (1). A broad band

appeared around 3348 cm-1 in both cases is attributed to the O-H stretching vibration of the hydroxyl

group of PVA. A sharp band at 1094 cm-1 corresponds to the symmetrical stretching C-O-C (in acetyl

group) present in the PVA backbone due to the unhydrolyzed acetate groups of poly (vinyl acetate). The

asymmetric N-H stretching vibration of the primary amide overlaps with the stretching vibrations O-H.


31

The aliphatic C-H stretching vibrations appear at 2923cm-1. A strong band at 1659cm -1 was observed

and can be attributed to the stretching carbonyl (C=O) groups in the carboxamide functional groups of

the PVA/ AAm hydrogel. The presence of strong bands at 1616 cm-1 corresponding to the asymmetric

bending N-H groups (26, 27). From FT-IR results, it can be concluded that the formation of PVA/AAm

copolymer using ionizing radiation was occurred.

Figure (1): FT-IR spectra of PVA and PVA/AAm hydrogels.

2. Thermal Stability of the Prepared PVA/AAm Hydrogel

Thermogravimetric analysis (TGA) is considered as the most important method for studying

the thermal stability of polymeric materials. It monitors the weight changes in a sample as a function

of temperature. The relative thermal stability of the different hydrogels was assessed by comparing the

weight change in the temperature range 0 –600 C and TGA data is shown in Figure (2) and presented

in Table (1). Pure PVA hydrogel shows a stable thermogram up to temperature of 211oC, beyond

which a smooth decrease in weight is observed. Whereas PVA/AAm hydrogel shows its famous four

degradation steps which due to the loss of associated water, anhydride formation, decarboxylation and

backbone degradation, respectively (28, 29). It can also be noted that, the thermal stability of the prepared

PVA/AAm hydrogel decreases as the AAm content increases in the hydrogel. The weight loss for

PVA/AAm hydrogel is lower than that of pure PVA hydrogel as shown in Table (1). The copolymer

hydrogel (PVA/AAm) of composition (70/30) possesses the highest thermal stability, which is almost

similar to that of pure PVA. The analysis of the thermograms shows that the PVA/AAm hydrogels are

relatively stable in the temperature range of 100–200 C, and the degradation of hydrogel is controlled

mainly by the composition of the hydrogel.


32

Table (1): Thermal parameters for PVA/AAm hydrogels at various compositions.

PVA/AAm

(wt%)

Tonst

(oC)

Char residue

(%)

Tg

(oC)

Tm

(oC)

H

(J/g)

100/0 211 4.6 79 225 49

70:30 210 9.3 91 210 45

50:50 201 10.3 94 206 30

30/70 200 11,6 99 204 22

* Tm is the Melting temperature

* Tg is the glass transition temperature

* H is the melting enthalpyt

Figure (2): TGA thermal diagrams of PVA/AAm hydrogels of various compositions.

3. Thermal Parameters

DSC thermal d foagramsr various compositions of PVA/AAm hydrogels were made and

shown in Figure (3). The thermal parameters of PVA/AAm hydrogels ; Tm ,Tg and ΔHm, were

evaluated and shown in Table (1). Pure PVA hydrogel has been exhibit an endothermic peak that

corresponds to the Tm at 225 ◦C. Both Tm and ΔHm decrease as the percentage of AAm increases in the

gel. The higher the AAm content in the hydrogel, the lower the values of Tm and ΔHm. The decrease in

ΔHm values of PVA/AAm hydrogels compared with the pure PVA can be attributed to the increase in


33

crosslinking network structure. In addition, the area under the melting peak decreases as the AAm

content increases. This indicates a smaller fraction of crystalline phase and a larger fraction of

amorphous phase, which may benefit anionic transition. The introducing of AAm into PVA caused

changes in the morphological structure in which the crystallinity domains in (PVA/AAm) decreases

due to the increase in crosslinking network formation that caused by radiation process. It is well

known that, below Tg, molecules do not have segmental motion, and some portions of the molecules

may not wiggle around, but may only be able to vibrate slightly. The Tg of pure PVA is about 79; by

the addition of AAm the Tg is slightly increased. This increase in Tg is due to the increase in

crosslinking network structure which decreases the segmental motion and the mobility of the chains.

Figure (3): DSC thermal diagrams of (a) PVA, PVA/AAm hydrogels of compositions; (b) 70/30, (c)

50/50 and (d) 30/70.

4. Swelling Studies

In order to evaluate the effect of PVA/AAm hydrogel network structure, the swelling behavior of

various compositions of PVA/AAm hydrogel as a function of time were carried out and shown in Figure

(4). It was found that the swelling capacity of the hydrogels increased with the decrease in AAm content

in PVA/AAm hydrogel , i.e. increases PVA content in network structure. This may be due to the

increase in crosslinking network structure of PVA/AAm hydrogel with increasing AAm contents in the

polymer sturcure as explained by DSC. Actually the hydrogen bonding due –OH groups of PVA tends to

crystallize the PVA chains through physical cross-linking which due to steric hindrance of the bulky

amide groups restricts the chains and decreases the crystallinity of PVA segments (30).

The effect of swelling medium on the swelling percent of PVA/AAm hydrogel was investigated

and shown in Figure (5). The swelling of PVA/AAm hydrogel was carried out in distilled water, pH of 2

and pH of 7 buffers. It can be observed that nearly equal swelling has been observed in distilled water,

pH 2 and pH 7 buffers.


34

Time (min)

0 200 400 1000 1200 1400

Sw

elli

ng (

%)

0

200

400

600

800

1000

100/0

70/30

50/50

30/70

PVA/AAm

Figure (4): Effect of time on the swelling percent of PVA/AAm hydrogels prepared at irradiation

dose of 20 kGy at room temperature.

Time (min)

0 200 400 1000 1200 1400

sw

elli

ng (

%)

0

200

400

600

800

1000

distilled water

buffer 2

buffer 7

Figure (5): Effect of the swelling medium on the swelling percent of PVA/AAm hydrogels of

composition (70/30) that prepared at irradiation dose of 20 kGy at room temperature.

5. Ketoprofen Uptake

Before the investigation of release experiment, the adsorption behavior of various

compositions of the prepared PVA/AAm hydrogels towards ketoprofen was investigated. The


35

hydrogels were swollen in ketoprofen solution of concentration 100 mg/L at pH 7. The amount of

ketoprofen adsorbed into 0.1 gm of PVA/AAm hydrogel was measured and given in Figure (6). It can

be seen that the uptake was decreased with increasing the AAm content in the hdrogel. The increase of

AAm in the hydrogel results in increasing the crosslinking network structure as confirmed by DSC

data. The swelling was found to be decreased by increasing the AAm content in the hydrogel which

impedes the interior of ketoprofen drug into the gel.

Hydrogel composition (%)

90 80 70 60 50 40 30 20

0.45

0.50

0.55

0.60

0.65

0.70

Dru

g u

pta

ke (

mg/m

l)

PVA

10 20 30 40 50 60 70 80 AAm

Figure (6): Effect of hydrogel composition on the ketoprofen uptake of initial concentration 200 mg/L

hydrogels prepared at irradiation dose 20kGy.

6. Release of Ketoprofen

6.1. Effect of pH

The in vitro release of ketoprofen from PVA/AAm hydrogel was investigated at various pH's of

medium and shown in Figure (7). It can be seen that the drug release increases with the increase in pH

of medium. At low pH, the release of such hydrogel decreases because there is a high H+ concentration

then H-bond is formed and the migration of drug molecules becomes low. In this case the hydrogel

can keep the solute because the texture structure becomes strong. Whatever, the acidic medium is not

suitable for releasing process of the drug.


36

pH

0 2 4 6 8 10

0.0

0.2

0.4

0.6

0.8

1.0

1.2D

rug

re

lea

se

(m

g/m

l)

Figure (7): Effect of pH on the ketoprofen release from PVA/AAm (70/30) hydrogel at initial

concentration 100 mg/L hydrogel prepared at irradiation dose 20kGy.

6.2. Effect of Time

Figure (8) shows the drug release behavior of various compositions of PVA/AAm hydrogels as

a function of time at pH 7. It can be seen that the release from PVA/AAm hydrogel increases

substantially with time up to 500 min and then tends to level off. The amount released depends upon

the composition of the hydrogel in the polymer matrix. It was found that the release of ketoprofen

increases as the PAAm content decreases in the hydrogel. This is possibly due to the formation of

lightly cross-linked PVA/AAm hydrogel given that the cross-linking process in that case takes place

between acrylamide and PVA which was confirmed by DSC. Also, increase the AAm content in

PVA/AAm hydrogels decreased the swelling capacity; therefore, the diffusion and liberation rate of

ketoprofen throughout the polymer matrix was decreased.

The mechanism of transporting the ketoprofen from PVA/AAm hydrogels was analyzed by the

Fick’s law (31).

The Fick’s law model is expressed as:

where n is the swelling exponent; k is the swelling rate front factor; and Wt and W∞ are the drug

release by the hydrogel at time t and the equilibrium time, respectively. A double-log plot of the

swelling ratio versus the time provides the value of n, which determines the nature of the solvent

diffusion process, that is, Fickian , non-Fickian diffusion kinetics or Super Case II models. When n ≤

0.5, the mechanism is Fickian type in which the sorption is diffusion controlled. When n ═ 1,

relaxation control occurs, leading to zero-order release. When the value of n is between 0.5 and 1, the

release follows non-Fickian diffusion, where the system will be diffusion and relaxation controlled. ln

F vs. ln t graphs are plotted for ketoprofen release from various compositions and shown in Figure (9).


37

The diffusion exponents (n) and diffusion constants (k) are calculated from the slopes and intercepts of

the lines, respectively, and listed in Table 2. The release of Ketoprofen at pH 7 showed the non-

Fickian mechanism for all investigated hydrogels which means the rate of diffusion of drug from the

polymer is comparable to rate of polymer chain relaxation. It can be said that, for higher swelling

values of the hydrogels, the transport of drug into the hydrogel matrix where the lower polymer

relaxation rate resulted in higher diffusion rate (32).

Time (min)

0 100 200 300 400 500 600 700

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

30/70

50/50

70/30

PVA /AAm

Dru

g r

ele

ase

(m

g/m

l)

Figure (8): Effect of time on the ketoprofen release from various compositions of PVA/AAm

hydrogel at pH 7 and initial concentration 100 mg/L

Figure (9): Swelling kinetic curve of PVA/AAm hydrogels as ln F versus ln t.


38

Table 1: Kinetic parameters of ketoprofen release at various compositions of PVA/AAm hydrogels

at pH 7

PVA/AAm (%) n k R2

30/70 0.75 0.2853 0.9825

50/50 0.72 0.4210 0.9770

70/30 0.76 0.4291 0.9862

6.3. Effect of Feed Concentration

The effect of initial drug concentration on the drug release was investigated and shown in

Figure (10). The increase in the initial drug concentration from 50 to 200 mg/L in the swelling

medium leads to increase the amount of release of drug. The reason for such result was attributed to

the specific bonding of positively charged drug with partially ionized groups of the hydrogel, and the

higher free volume available for diffusion.

Drug concentration (mg/ml)

0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2

Dru

g r

ele

ase

(m

g/m

l)

0.0

0.2

0.4

0.6

0.8

1.0

Figure (10): Effect of ketoprofen concentration on the release from PVA/AAm (70/30) hydrogel at

pH 7.

CONCLUSION

In this study, various compositions of PVA/AAm hydrogel of total concentration 20% was

prepared by gamma radiation at irradiation dose of 20 kGy. The thermal stability and swelling percent

of the prepared hydrogel decreased as the AAm content increased in the hydrogel. Both Tm and ΔHm

decreased as the percentage of AAm increased in the gel and the PVA/AAm hydrogel of composition

(70/30) possesses the highest thermal stability. The release of ketoprofen drug from the PVA/AAm

hydrogel was studied and showed that the release of ketoprofen increased as the PAAm content


39

decreased in the hydrogel. The release of ketoprofen followed a non-Fickian type and the acidic

medium is not suitable for releasing process of the drug. The increase in the initial drug concentration

leads to increase the amount of ketoprofen releasing. It is suggested that such prepared hydrogel is of

practical interest in the field of drug delivery system under control release as it possessed that pH

stimuli- responsive character.

REFERENCES

(1) D. Yang, Y. Li, J. Nie, Preparation of gelatin/PVA nanofibers and their potential application in

controlled release of drugs, Carbohyd. Polym. 69 (2007) 538.

(2) R.G. Loughlin, M.M. Tunney, R.F. Donnelly, D.J. Murphy, M. Jenkins, P.A. McCarron,

Modulation of gel formation and drug-release characteristics of lidocaine-loaded poly(vinyl

alcohol)-tetraborate hydrogel systems using scavenger polyol sugars, Eur. J. Pharm. Biopharm.

69 (2008) 1135.

(3) S. Kundakci, E. Karadağ, Ö. B. Üzüm, Investigation of Swelling/Sorption Characteristics of

Highly Swollen AAm/AMPS Hydrogels and Semi IPNs with PEG as Biopotential Sorbent, J.

Encaps. Adsorp. Sci. 1 (2011) 7.

(4) A. Roy, J. Bajpai, A. K. Bajpai, Dynamics of controlled release of chlorpyrifos from swelling

and eroding biopolymeric microspheres of calcium alginate and starch, Carbohyd. Polym.76( 2)

(2009) 222

(5) Y. Qiu, K. Park, Environment-sensitive hydrogels for drug delivery, Adv. Drug Delivery Rev. 53

(2001) 321.

(6) J. Varshosaz, N. Koopaie, Cross-linked Poly (vinyl alcohol) Hydrogel: Study of swelling and

drug release behaviour, Iran. Polym. J. 11(2) (2002), 123.

(7) S.J. Kim, S.J. Park, T.D. Chung, K.H. An, S.I. Kim, Properties of interpenetrating polymer

network hydrogels compound of poly(vinyl alcohol) and poly(N-isopropy-lacrylamide), J. Appl.

Polym. Sci. 89 (2003) 2041.

(8) T. Wang, M. Turhan, S. Gunasekaran, Selected properties of pH-sensitive, biodegradable

chitosan-poly(vinyl alcohol) hydrogel, Polym. Int. 53 (2004), 911.

(9) H. B. Senturk, C.E. Macias, J. H. Kung, O.K. Muratoglu, Poly(vinyl alcohol)–acrylamide

hydrogels as load-bearing cartilage substitute, Biomaterials 30 (2009) 589.

(10) C.M. Hassan, N.A. Peppas, Structure and applications of poly(vinyl alcohol) hydrogels produced

by conventional crosslinking or by freezing /thawing methods, Advances in polymer science,

153 (2000) 38.

(11) J. Lu, Q. Nguyen, J. Zhou, Z.H. Ping, Poly(vinyl alcohol)/poly(vinyl pyrrolidone)

interpenetrating polymer network: Synthesis and pervaporation properties, J. Appl. Polym. Sci.

89 (2003) 2808.

(12) K.R. Park, Y.C. Nho, Preparation and characterization by radiation of hydrogels of PVA and

PVP containing Alovera, J. Appl. Polym. Sci. 91, (2004) 1612.

(13) S.G. Abd Alla, R. H. Helal, A. F. Wasfy, A.M. El-Naggar, structure-property and swelling

behavior of electron beam irradiated poly(vinyl alcohol)/acrylamide/sodium montmorillonite clay

composites, J. Appl. Polym. Sci. 121 (2011) 2634

(14) L.C. Lopérgolo, A.B. Luga, L.H. Catalani, direct UV photocross-linking of poly(N-vinyl-2-

pyrrolidone) (PVP) to produce hydrogels, Polymer 44 (2003) 6217.

(15) S.F. Mohamed , G.A. Mahmoud, M.F. Abou Taleb, Synthesis and characterization of

poly(acrylic acid)-g-sodium alginate hydrogel initiated by gamma irradiation for controlled

release of chlortetracycline HCl., Monatsh. Chem. 144 (2013) 129.

(16) H. Yang, W. Song, Y. Zhuang, X. Deng, Synthesis of Strong Electrolyte Temperature-Sensitive

Hydrogels by Radiation Polymerization and Application in Protein Separation, Macromol. Biosci.

3 (2003) 400.


40

(17) G. A. Mahmoud, S. E. Abdel-Aal, N. A. Badway, S. A. Abo Farha, E. A. Alshafe, Radiation

synthesis and characterization of starch-based hydrogels for removal of acid dye, Starch/Stärke

65 (2013) 1.

(18) S. Francis, D. Mitra, B.R. Dhanawade, L. Varshney, S. Sabharwal, Gamma radiation synthesis of

rapid swelling superporous polyacrylamide hydrogels, Radiat. Phys. Chem. 78 (2009) 951.

(19) M. Nagpal, S. K. Singh , D. Mishra, Synthesis characterization and in vitro drug release from

acrylamide and sodium alginate based superpours hydrogel device , Int. J. Pharm. Investig.3(3)

(2013) 131.

(20) F. Becerra-Bracamontes, J. C. Sánchez-Díaz, A. González-Álvarez, P. Ortega-Gudiño, E.

Michel-Valdivia, A. Martínez-Ruvalcaba, Design of a drug delivery system based on

poly(acrylamide-co-acrylic acid)/chitosan nanostructured hydrogels, j. Appli. Polym. Sci. 106(6)

(2007) 3939.

(21) M.S. Rihawy , A. Alzier, A.W. Allaf, PIXE investigation of in vitro release of chloramphenicol

across polyvinyl alcohol/acrylamide hydrogel, Nucl. Instrum. Methods Phys. Res., Sect. B 269

(2011) 1892.

(22) C.A. Heyneman, C. Lawless-Liday, G.C. Wall, Oral versus topical NSAIDs in rheumatic disease:

a comparison. Drugs 60 (2006) 555.

(23) M.L. Vueba, M.E. Pina, F. Veiga, J.J. Sousa, L.A.E. Batista de Carvalho, Conformational study

of ketoprofen by combined DFT calculations and Raman spectroscopy, Int. J. Pharm. 307(2006)

56.

(24) M. Silion, D. Hritcu, I.M. Jaba, B. Tamba, D. Ionescu, O. C. Mungiu, I. M. Popa, In vitro and in

vivo behavior of ketoprofen intercalated into layered double hydroxides, J. Mater. Sci. Mater

Med. 21(2010) 3009.

(25) Z. S. Akdemir, N. Kayaman-Apohan, Investigation of swelling, drug release and diffusion

behaviors of poly(N- sopropylacrylamide)/poly (N-vinylpyrrolidone) full-IPN hydrogels, Polym.

Adv. Technol. 18(2007) 932.

(26) T.M. Aminabhavi, H.G. Naik, Synthesis of graft copolymeric membranes of poly(vinyl alcohol)

and polyacrylamide for pervaporation separation of water/acetic acid mixtures, J. Appl. Polym.

Sci. 83 (2002) 244.

(27) R.F. Bhajantri, V. Ravindrachary, A. Harisha, V. Crasta , S. P. Nayak , B. Poojary,

Microstructural studies on BaCl2 doped poly(vinyl alcohol) Polymer 47 (2006) 3591.

(28) P. Cerrai, G.D. Guerra, S. Maltinti, M. Tricoli, Physicochemical properties of

poly(allylammonium acrylate) complexes obtained by radical template polymerization,

Macromol. Rapid. Commun. 15(1994) 983.

(29) P. Cerrai, G.D. Guerra, S. Maltinti, M. Tricoli, Polyelectrolyte complexes obtained by radical

polymerization in the presence of chitosan, Macromol. Chem. Phys. 179 (1996) 3567.

(30) B. Singh, L. Pal, Radiation crosslinking polymerization of sterculia polysaccharide–PVA–PVP

for making hydrogel wound dressings, Int. J. Biol. Macromol. 48 (2011) 501–510.

(31) A. K. Bajpai, M. Sharma, Preparation and characterization of novel pH-sensitive binary grafted

polymeric blends of gelatin and poly(vinyl alcohol): Water sorption and blood compatibility

study. J. Appl. Polym. Sci., 100 (2006) 599.

(32) N. A. Maziad, S. E. Abd El-Aal, N. A. El-Kelesh, Equilibrium Adsorption Isotherm and

Controlled Release of Antibiotic Drug Chloroamphenicol from Poly(2-vinyl pyridine/acrylic

acid) Hydrogels Prepared by Gamma Radiation, J. Appl.Polym. Sci. 111(2009) 1369.

http://www.ncbi.nlm.nih.gov/pubmed/?term=Nagpal%20M%5Bauth%5D

http://www.ncbi.nlm.nih.gov/pubmed/?term=Singh%20SK%5Bauth%5D

http://www.ncbi.nlm.nih.gov/pubmed/?term=Mishra%20D%5Bauth%5D

Documents

In-Vitro Release of Ketoprofen Behavior Loaded in ...3) Dalia Hegazy Paper 1.pdfIn-Vitro Release of Ketoprofen Behavior Loaded in Polyvinyl Alcohol / Acrylamide Hydrogels Prepared